Gyrate atrophy of the choroid and retina with hyperornithinemia has been described in 30 patients. We have recently examined four such patients and have demonstrated deficient activity of ornithine ketoacid aminotransferase (OKT) in fibroblasts from all. Detailed opthalmologic examination of these patients will be completed and psychometric testing and electrophysiological and neurological evaluation will be performed. Skin and muscle biopsies will be examined by light and electron microscopy. Amino acids will be quantitated in fasting plasma and 24 hr. urine samples and adrenal clearance of these substances determined. The effect of pharmacologic doses of vitamin B6 on patients will be determined by studying clinical and biochemical parameters. L-ornithine (5-3H) will be synthesized and used in the development of a radiochemical assay for OKT activity. Characteristics of the normal human liver enzyme, including substrate affinity and specificity, will be determined. Utilizing this assay, the level of OKT activity in fibroblast from normal subjects, patients, and obligate carriers will be established. The effect of various concentrations of co-enzyme, pyridoxal phosphate will be determined. Detection of heterozygotes in other family members will be performed and linkage analysis carried out after examination of blood and saliva for common genetic polymorphisms. With the intention of developing an animal model for this disease, several potential inhibitors of OKT will be synthesized and tested in the radiochemical assay. The specificity of these inhibitors will be determined and their toxicity to skin fibroblasts evaluated. Several species of animals will be treated for periods of 6-12 months with these inhibitors, with and without an ornithine supplemented diet. The animals will be followed with periodic fundus examination, electroretinography and measurment of plasma ornithine. If changes are demonstrable, fundus photography and fluorescein angiography will be attempted. At intervals determined by the findings, the animals will be sacrificed and ocular and nonocular tissues will be examined histologically.